1. Field of the Invention
The present invention concerns a novel GTP binding protein (Smg p21) which gives an inhibitory effect on ras oncogene products, and a method for producing said protein by utilizing recombinant DNA technology.
2. The Prior Art
Each of cells constituting an individual mammal play its own role in such a fashion that the cell always receives extracellular information or stimulation, and responses thereto.
An information conversion unit on a cell membrane for receiving information given to each of cells by so-called primary information-transmitting substance consists of three kinds of proteins, i.e., a receptor, a transducer and an effector. GTP (guanosine-5-triphosphate) binding protein (hereinafter referred to as "G protein") functions as the transducer among them. That is, when the receptor receives primary information from outside of a cell, it acts on an inactive GDP-G protein, by which the GDP bonded to G protein is converted into GTP to form an active GTP-G protein. Then, the active GTP-G protein gives an effect on the effector and information (secondary information) is transmitted from the effector to the inside of the cell.
For the G protein, there have been known, for example, functions of high molecular weight G protein (molecular weight of about 40,000) consisting of various proteins (subunits). Recently, the presence of low molecular weight G protein has been revealed.
There are present at least 15 kinds of the low molecular weight G proteins, i.e., G proteins with molecular weight of from 20,000 to 25,000. The present inventors have previously succeeded in purifying G protein with molecular weight of 24,000 (Smg p25A) and G protein with molecular weight of 22,000 (Smg p21:22K dalton) as single protein in SDS-PAGE and reported details for the G protein of Smg p25A (refer to Experimental Medicine, vol. 6, No. 5, p 34-42, 1988: Journal of the Biological Chemistry, 263, p 2897-2904, 1988).
However, the structure and function of such G proteins have not yet been revealed in detail.
Furthermore, Smg p21 can be purified only by an amount of about several tens of micrograms by using a conventional methodology in protein chemistry. Accordingly, it has been difficult to use them in a great amount for the pharmaceutical test such as of anti-cancer agents. Further, it has still been considered impossible to introduce artificial mutation, thereby preparing Smg p21 variant protein with a high anti-ras activity.